CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms.
CD1
T cell receptor
T cells
antigen presentation
antigen processing
dendritic cells
lipidomics
major histocompatibility complex
sphingolipids
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
12 10 2023
12 10 2023
Historique:
received:
16
09
2021
revised:
05
05
2023
accepted:
21
08
2023
pmc-release:
12
10
2024
medline:
26
10
2023
pubmed:
20
9
2023
entrez:
19
9
2023
Statut:
ppublish
Résumé
The CD1 system binds lipid antigens for display to T cells. Here, we solved lipidomes for the four human CD1 antigen-presenting molecules, providing a map of self-lipid display. Answering a basic question, the detection of >2,000 CD1-lipid complexes demonstrates broad presentation of self-sphingolipids and phospholipids. Whereas peptide antigens are chemically processed, many lipids are presented in an unaltered form. However, each type of CD1 protein differentially edits the self-lipidome to show distinct capture motifs based on lipid length and chemical composition, suggesting general antigen display mechanisms. For CD1a and CD1d, lipid size matches the CD1 cleft volume. CD1c cleft size is more variable, and CD1b is the outlier, where ligands and clefts show an extreme size mismatch that is explained by uniformly seating two small lipids in one cleft. Furthermore, the list of compounds that comprise the integrated CD1 lipidome supports the ongoing discovery of lipid blockers and antigens for T cells.
Identifiants
pubmed: 37725977
pii: S0092-8674(23)00912-1
doi: 10.1016/j.cell.2023.08.022
pmc: PMC10591967
mid: NIHMS1932598
pii:
doi:
Substances chimiques
Antigens, CD1
0
Lipids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4583-4596.e13Subventions
Organisme : NIAID NIH HHS
ID : R21 AI115358
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92020D00005
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93022D00005
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93023D00005
Pays : United States
Organisme : NIDA NIH HHS
ID : 75N95020D00005
Pays : United States
Organisme : ORFDO NIH HHS
ID : 75N99020D00005
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI049313
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR048632
Pays : United States
Organisme : Wellcome Trust
ID : 209222/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008
Pays : United Kingdom
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors hold intellectual property through the Massachusetts General Brigham (D.B.M., G.S.O., and J.R.; filing 29618-0390P01) and the University of Oxford (G.S.O., C.S.H., and Y.-L.C.; filings 2116709.3, 2217923.8, 2217924.6). G.S.O. collaborates with UCB and Janssen, and D.B.M. consults for Pfizer.
Références
Science. 2004 Jan 23;303(5657):523-7
pubmed: 14684827
J Clin Invest. 2021 Jan 4;131(1):
pubmed: 33393500
Nat Immunol. 2005 Aug;6(8):819-26
pubmed: 16007090
Nat Immunol. 2002 May;3(5):435-42
pubmed: 11938350
J Biol Chem. 1957 May;226(1):497-509
pubmed: 13428781
J Clin Invest. 1995 Mar;95(3):1281-7
pubmed: 7883976
Nature. 1994 Dec 15;372(6507):691-4
pubmed: 7527500
Science. 1992 Mar 6;255(5049):1261-3
pubmed: 1546328
J Immunol. 2009 Apr 15;182(8):4784-91
pubmed: 19342656
Eur J Immunol. 1979 Mar;9(3):205-10
pubmed: 376318
J Exp Med. 2007 May 14;204(5):1131-44
pubmed: 17485514
J Exp Med. 2004 Mar 1;199(5):649-59
pubmed: 14981115
Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23671-23681
pubmed: 31690657
Nat Immunol. 2010 Dec;11(12):1102-9
pubmed: 21037579
J Exp Med. 2008 May 12;205(5):1201-11
pubmed: 18443227
Front Immunol. 2022 Jul 07;13:897873
pubmed: 35874748
Nature. 1996 Nov 14;384(6605):134-41
pubmed: 8906788
Chem Biol. 2011 Dec 23;18(12):1537-49
pubmed: 22195556
Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1266-75
pubmed: 26884207
Nature. 2007 Jul 5;448(7149):44-9
pubmed: 17581592
Science. 2005 Nov 25;310(5752):1321-4
pubmed: 16311334
Nature. 1993 Jul 1;364(6432):33-9
pubmed: 8316295
EMBO Rep. 2020 Jun 4;21(6):e48927
pubmed: 32363653
Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17755-60
pubmed: 22006319
J Exp Med. 2011 Aug 29;208(9):1741-7
pubmed: 21807869
EMBO J. 2002 Feb 15;21(4):825-34
pubmed: 11847129
Nature. 1987 Sep 17-23;329(6136):251-4
pubmed: 3114646
Annu Rev Immunol. 1993;11:213-44
pubmed: 8476560
Nat Commun. 2019 Jan 4;10(1):56
pubmed: 30610190
Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19335-40
pubmed: 22087000
J Exp Med. 2000 Jul 17;192(2):281-8
pubmed: 10899914
Nat Rev Immunol. 2015 Oct;15(10):643-54
pubmed: 26388332
Nat Immunol. 2003 Aug;4(8):808-15
pubmed: 12833155
Science. 1997 Oct 10;278(5336):283-6
pubmed: 9323206
Curr Protoc. 2021 Feb;1(2):e36
pubmed: 33539685
J Immunol. 2007 May 15;178(10):6280-9
pubmed: 17475856
EMBO J. 2002 Apr 2;21(7):1650-60
pubmed: 11927549
Elife. 2020 Apr 17;9:
pubmed: 32301705
Sci Immunol. 2017 Oct 20;2(16):
pubmed: 29054999
Immunity. 1998 Mar;8(3):341-51
pubmed: 9529151
Nature. 1991 Oct 17;353(6345):622-7
pubmed: 1656276
Nat Immunol. 2019 Dec;20(12):1644-1655
pubmed: 31636468
PLoS One. 2009;4(5):e5325
pubmed: 19415116
Nat Immunol. 2002 Aug;3(8):721-6
pubmed: 12118248
Angew Chem Int Ed Engl. 2020 May 4;59(19):7555-7560
pubmed: 32067294
J Immunol. 2013 Nov 1;191(9):4499-503
pubmed: 24089190
Nature. 2005 Mar 24;434(7032):525-9
pubmed: 15791258
Nat Rev Immunol. 2018 May;18(5):325-339
pubmed: 29292391
Nucleic Acids Res. 2018 Jul 2;46(W1):W363-W367
pubmed: 29860391
J Exp Med. 2021 Jul 5;218(7):
pubmed: 33961028
Nature. 2005 Mar 24;434(7032):520-5
pubmed: 15791257
Immunity. 1999 Dec;11(6):743-52
pubmed: 10626896
Curr Opin Immunol. 2004 Feb;16(1):90-5
pubmed: 14734115
J Biol Chem. 2021 Oct;297(4):101197
pubmed: 34536421
Nature. 1987 Oct 8-14;329(6139):512-8
pubmed: 2443855
Science. 1995 May 12;268(5212):863-5
pubmed: 7538697
Nature. 1987 Oct 8-14;329(6139):506-12
pubmed: 3309677
Immunity. 2010 Dec 14;33(6):853-62
pubmed: 21167756
Annu Rev Immunol. 1998;16:323-58
pubmed: 9597133
J Exp Med. 2013 Apr 8;210(4):729-41
pubmed: 23530121
EMBO J. 2005 Sep 21;24(18):3159-65
pubmed: 16138081
Mol Immunol. 2015 Dec;68(2 Pt A):94-7
pubmed: 26141240
Nat Immunol. 2012 Mar 18;13(5):474-80
pubmed: 22426352
J Biol Chem. 2011 Oct 28;286(43):37692-701
pubmed: 21900247
Immunity. 2008 Jun;28(6):774-86
pubmed: 18538591
Nat Immunol. 2018 Apr;19(4):397-406
pubmed: 29531339
Nat Commun. 2016 Oct 27;7:13257
pubmed: 27807341
Nature. 1990 Nov 15;348(6298):252-4
pubmed: 1700304
Nat Immunol. 2014 Feb;15(2):177-85
pubmed: 24362891
Science. 1997 Nov 28;278(5343):1626-9
pubmed: 9374463
Science. 1998 Mar 6;279(5356):1541-4
pubmed: 9488653
Science. 1996 Oct 11;274(5285):209-19
pubmed: 8824178
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3052-7
pubmed: 20133624
EMBO J. 2006 Jul 12;25(13):2989-99
pubmed: 16794581
Nat Immunol. 2015 Mar;16(3):258-66
pubmed: 25642819
Science. 1997 Jul 18;277(5324):339-45
pubmed: 9219685